Aging-Related Lateral Ventricular Shape Changes and Corresponding Mechanical Loading Derived from Longitudinal Image Registration

Abstract Lateral ventricular enlargement is one of the most prominent features of the aging brain and is clearly visible on structural magnetic resonance imaging. In addition, ventricular volume increases significantly faster in neurodegenerative diseases in comparison to healthy aging and, therefore, is a very suitable diagnostic marker for Alzheimer’s disease and related dementias. Age-dependent ventricular volume has been quantified based on cross-sectional data and short-term volume changes have been extracted from longitudinal imaging for selective subject groups. Strikingly, however, we only have a limited understanding of ventricular shape changes and the corresponding mechanical loads that act on the ventricular wall and increase with age. Therefore, we propose a framework that uses nonlinear registration to quantify subject-specific brain deformations between two longitudinal scans, maps the resulting warp field onto a ventricular surface template mesh, and quantifies mechanical loading measures including displacement magnitude, curvature change, area stretch, and maximum principal wall strain. From the Alzheimer’s Disease Neuroimaging Initiative, we selected a cohort of 50 cognitively normal subjects aged 70 - 75 years at baseline and with a follow-up scan 4 - 5 years later. In this group, we observed mostly uniform expansion of the lateral ventricles with an average displacement magnitude of 0.88 ± 0.3 mm across the whole ventricle. Given the shape of the lateral ventricle, however, significant sections of the ventricular wall experience high mechanical loads with respect to our mechanomarkers. Specifically, maximum mechanical loading consistently localizes along the ventricular edges and atrium while the ventricle’s main body exhibits minimal loading. Based on the cohort included in this study, we did not observe sex-based di↵erences with respect to any mechanomarker, noticed that on average 29.2 ± 9.3% of the ventricular wall experience wall area increase, and that on average only 4.4 ± 2.5% of the ventricular wall experience wall shrinking. Interestingly, these locations of pronounced shape change and peak mechanical loading coincide with typical periventricular white matter lesion sites. This suggests that age-related ventricular enlargement is intricately linked to white matter degeneration and corresponding cognitive decline.